melatonin and flecainide loxitane

6A-B: Number of episodes of OREM/DREM phases in narcoleptic mice (Ox−/−) treated by modafinil/flecainide (FIG. Some reports may have incomplete information.Patients can bring a copy of the report to their healthcare provider to ensure that all drug risks and benefits are fully discussed and understood. The transfer of fluorochrome by gap junctions (composed of connexins) is evaluated by flow cytometry (1A and 1B). . GJB6 (Cx30), GJB1 (Cx32), GJB2 (Cx26), GJA5 (Cx40) and GJA1 (Cx43) open reading frames were amplified from human cDNA. The wake duration was measured using polygraphic analyses.FIG. Between each test, the unit is cleaned with a cloth soaked in water and alcohol to avoid olfactory detection.

More precisely, the term “Modafinil” herein designates any form of modafinil (racemate, R-modafinil, S-modafinil, etc. In addition, higher inhibition levels are reached for glial connexins Cx26, Cx30 and Cx43.Preclinical and clinical data indicated that modafinil modifies sleep-cycle rhythm and promotes wake phases (Lin et al, 2008). 5A. The renal clearance of the two enantiomers was, however, comparable and similar to that observed in the EM subjects. . This synergistic activity could be explained by the fact that flecainide strongly extends the duration of Modafinil treatment (example 4). In a preferred embodiment, the present invention thus pertains to flecainide, for use for potentiating the promnesiant and/or awakening effects of modafinil, and/or for improving its safety, and/or for increasing the duration of action of modafinil in patients in need thereof, especially in patients suffering from: excessive daytime sleepiness (EDS), sleep disorders, insufficient sleep time, central sleep apnea, narcolepsy (with or without cataplexy), obstructive sleep apnea/hypopnea (SAHOS), idiopathic hypersomnia, Kleine-Levin syndrome, circadian rhythm disorders, shift work sleep disorder, jet-lag, disorders after sleep restriction or sleep deprivation (attention disorders, alertness disorders, sleepiness), restless legs syndrome (RLS) and Periodic Lim Movement Disorders (PLMD), insomnia, parasomnia, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), disorders commonly associated with somnolence or sleepiness (such as Parkinson disease, multiple sclerosis, stroke, neuromuscular disorders or structural brain disorders, respiratory disorders, chronic renal failure, liver failure, rheumatologic disorders), medication-induced somnolence (due to benzodiazepines, barbiturates, sleeping pills, antidepressants, anti-psychotics .

Consult your healthcare professional (e.g., doctor or pharmacist) for more in formation.Selected from data included with permission and copyrighted by First Databank, Inc. Using a sub-efficient dosage of modafinil (32 mg/kg), the inventors demonstrated a new feature of the combination of modafinil and flecainide since it significantly increases the total duration of wake episodes.Wild-type C57bl/6 male mice (n=9/groups) were implanted with EEG/EMG/EOG electrodes for polysomnographic analyses. The results are shown in FIG. 24, 2013, the entire disclosures of which are hereby incorporated by reference.The present invention relates to the use of flecainide as an anti-connexin agent. In particular, the connexins 26 (Cx 26), 30 (Cx 30), 30.2 (Cx30.2), 32 (Cx 32), 36 (Cx 36), 37 (Cx 37), 40 (Cx 40), 43 (Cx 43), 45 (Cx 45), 46 (Cx 46), and 47 (Cx 47) are expressed in human on cells of the Central or Peripheral Nervous System (Nakase & Naus, 2004).The present inventors observed that flecainide is effective for inhibiting gap junctions made of all connexin they tested. Cells were rinsed in PBS and grown 24 h in fresh medium. 2A-B: Efficiency of flecainide for potentiating the awakening effect of modafinil. 5A.In a final aspect, the present invention relates to a combination product comprising flecainide and modafinil, for simultaneous, separated or staggered use for preventing and/or treating excessive daytime sleepiness (EDS), narcolepsy (with or without cataplexy), obstructive sleep apnea/hypopnea (SAHOS), shift work sleep disorder, restless leg syndrome, hypersomnia, idiopathic hypersomnia and fatigue, notably due to cancer, jet-lag, neurodegenerative disorders, menopause, traumatic brain injuries, viral infection or post-myelitis, or to fibromyalgia. 5C. Commissariat a L'Energie Atomique et Aux Energies Alternatives (Paris, FR) The administration can also be performed at different sites.

6B). In particular, and as disclosed in the experimental part below, flecainide is effective for inhibiting gap junctions made of connexin Cx40, Cx26, Cx30, Cx32, and/or Cx43. . Here we tested in rodents whether such activity was potentiated by flecainide after oral challenge with modafinil, using polysomnographic analysis on implanted mice. The index memory is represented by the average of alternating percentage (number of alternation choices/total number of tests X 100). These electrical signals cause the two pairs of heart chambers (left and right arteria and ventricles) to contract in a regular manner to produce regular heartbeats. ... Mexiletine is predicted to increase the exposure to loxapine. More specifically, it is used to regulate the rate and rhythm of the heart.

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